Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14878 | 44857;44858;44859 | chr2:178624648;178624647;178624646 | chr2:179489375;179489374;179489373 |
| N2AB | 13237 | 39934;39935;39936 | chr2:178624648;178624647;178624646 | chr2:179489375;179489374;179489373 |
| N2A | 12310 | 37153;37154;37155 | chr2:178624648;178624647;178624646 | chr2:179489375;179489374;179489373 |
| N2B | 5813 | 17662;17663;17664 | chr2:178624648;178624647;178624646 | chr2:179489375;179489374;179489373 |
| Novex-1 | 5938 | 18037;18038;18039 | chr2:178624648;178624647;178624646 | chr2:179489375;179489374;179489373 |
| Novex-2 | 6005 | 18238;18239;18240 | chr2:178624648;178624647;178624646 | chr2:179489375;179489374;179489373 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs1376059487  |
-0.676 | 0.989 | N | 0.488 | 0.299 | 0.310458034454 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/G | rs1376059487 |
-0.676 | 0.989 | N | 0.488 | 0.299 | 0.310458034454 | gnomAD-4.0.0 | 1.59384E-06 | None | None | None | None | N | None | 0 | 2.29085E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/K | rs1456271454 |
-0.155 | 0.37 | N | 0.176 | 0.177 | 0.388495093706 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/K | rs1456271454 |
-0.155 | 0.37 | N | 0.176 | 0.177 | 0.388495093706 | gnomAD-4.0.0 | 6.58207E-06 | None | None | None | None | N | None | 2.41418E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.736 | likely_pathogenic | 0.6496 | pathogenic | -0.059 | Destabilizing | 0.983 | D | 0.497 | neutral | None | None | None | None | N |
| R/C | 0.5541 | ambiguous | 0.4624 | ambiguous | -0.18 | Destabilizing | 1.0 | D | 0.62 | neutral | None | None | None | None | N |
| R/D | 0.9306 | likely_pathogenic | 0.8951 | pathogenic | -0.019 | Destabilizing | 0.998 | D | 0.553 | neutral | None | None | None | None | N |
| R/E | 0.6425 | likely_pathogenic | 0.576 | pathogenic | 0.055 | Stabilizing | 0.983 | D | 0.511 | neutral | None | None | None | None | N |
| R/F | 0.8865 | likely_pathogenic | 0.8396 | pathogenic | -0.223 | Destabilizing | 0.999 | D | 0.607 | neutral | None | None | None | None | N |
| R/G | 0.645 | likely_pathogenic | 0.5294 | ambiguous | -0.276 | Destabilizing | 0.989 | D | 0.488 | neutral | N | 0.453729643 | None | None | N |
| R/H | 0.3134 | likely_benign | 0.2425 | benign | -0.744 | Destabilizing | 0.999 | D | 0.558 | neutral | None | None | None | None | N |
| R/I | 0.6553 | likely_pathogenic | 0.5381 | ambiguous | 0.48 | Stabilizing | 0.999 | D | 0.622 | neutral | D | 0.532257251 | None | None | N |
| R/K | 0.1857 | likely_benign | 0.1718 | benign | -0.113 | Destabilizing | 0.37 | N | 0.176 | neutral | N | 0.488143904 | None | None | N |
| R/L | 0.5718 | likely_pathogenic | 0.4761 | ambiguous | 0.48 | Stabilizing | 0.992 | D | 0.488 | neutral | None | None | None | None | N |
| R/M | 0.6308 | likely_pathogenic | 0.5186 | ambiguous | 0.047 | Stabilizing | 1.0 | D | 0.5 | neutral | None | None | None | None | N |
| R/N | 0.8967 | likely_pathogenic | 0.8344 | pathogenic | 0.147 | Stabilizing | 0.998 | D | 0.566 | neutral | None | None | None | None | N |
| R/P | 0.9579 | likely_pathogenic | 0.9319 | pathogenic | 0.322 | Stabilizing | 0.999 | D | 0.57 | neutral | None | None | None | None | N |
| R/Q | 0.2207 | likely_benign | 0.1807 | benign | 0.042 | Stabilizing | 0.995 | D | 0.593 | neutral | None | None | None | None | N |
| R/S | 0.8192 | likely_pathogenic | 0.7312 | pathogenic | -0.26 | Destabilizing | 0.978 | D | 0.529 | neutral | N | 0.505140808 | None | None | N |
| R/T | 0.5916 | likely_pathogenic | 0.47 | ambiguous | -0.042 | Destabilizing | 0.997 | D | 0.501 | neutral | N | 0.50863835 | None | None | N |
| R/V | 0.6877 | likely_pathogenic | 0.5938 | pathogenic | 0.322 | Stabilizing | 0.998 | D | 0.607 | neutral | None | None | None | None | N |
| R/W | 0.5186 | ambiguous | 0.3876 | ambiguous | -0.229 | Destabilizing | 1.0 | D | 0.621 | neutral | None | None | None | None | N |
| R/Y | 0.8221 | likely_pathogenic | 0.755 | pathogenic | 0.173 | Stabilizing | 0.999 | D | 0.567 | neutral | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.